Ammonia → 2-Chloro-9-(tetrahydropyran-2-yl)adenine

HRID 527761Notes

Reaction equation

HRID 527761 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[C:4](Cl)[N:3]=1.[NH3:18].O>C(O)(C)C>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[C:4]([NH2:18])[N:3]=1

Participants

5

Reactant 3

HCID 222Ammonia2×HCID 962WaterHCID 2702652,6-Dichloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Product 1

HCID 127778192-Chloro-9-(tetrahydropyran-2-yl)adenine

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent2×

Procedure

2,6-Dichloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (36.9 g) was heated with 2M ammonia in isopropanol (250 ml) at 50° C. for 5 hours. After standing at ambient temperature overnight, a further quantity of 2M ammonia in isopropanol (100 ml) was added to break up the resultant cake and the reaction mixture was heated for a further 9 hours until the reaction was complete. To the reaction mixture was added water (70 ml) and the yellow solid filtered off. The solid was washed with isopropyl alcohol:water (5:1 (v/v), 60 ml) and then air-dried under suction to give a first crop. The filtrate was re-filtered after standing overnight to isolate precipitate and both solids were dried in vacuo. The first crop was pure with the second crop material showing a very minor impurity (isolated broad signal 3.5 ppm not seen in first crop) but was otherwise identical. Solid first crop (28.4 g), solid second crop (3.42 g).

Workup

  1. temperaturethe reaction mixture was heated for a further 9 hours until the reaction
  2. filtrationthe yellow solid filtered off
  3. washThe solid was washed with isopropyl alcohol:water (5:1 (v/v), 60 ml)
  4. customair-dried under suction
  5. customto give a first crop
  6. filtrationThe filtrate was re-filtered
  7. waitafter standing overnight
  8. customto isolate precipitate
  9. customboth solids were dried in vacuo
  10. customisolated broad signal 3.5 ppm not

Sources & evidence

ORD record
ord-da8746bc8942462db4bcc4123a7ec03a
Source dataset
uspto-grants-2016_05
Patent number
US09346806B2

Reaction notes

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